Cancer Center Program Memberships

Research Summary

I have spent 33 years doing research in therapeutic sciences and biotechnology development, first 16 years at Genentech and then 8 years at Sunesis (a company I founded) prior to joining UCSF 9 years ago. At Genentech, my group was among the first to develop gain-of-function engineering of enzymes and proteins by site-directed mutagenesis and phage display. At Sunesis, we developed novel technologies for fragment-based drug discovery, notably the site-directed approach Tethering. My lab at UCSF has developed the N-terminomics technology to characterize the caspase products cleaved during apoptosis. We currently have what we believe is the largest database of proteins that are cleaved by caspases (~2,000 targets in all), as well as targets cleaved in specific cells and their precise cleavage sites identified. More recently, we have extended our proteomics work to serum using the subtiligase tagging technology. This has allowed us to dive to very low abundance proteins in serum. We have also engineered a new small molecule activated protease, called the SNIPer. We have built a catalytic tagging device called the NEDDylator to interrogate molecular binding partners in cellular pathways involving E3 ligases. Recently, we have developed a motif-specific scaffold strategy for producing synthetic monoclonal antibodies specific to post-translational modifications. I am also Director of the Small Molecule Discovery Center (SMDC) at UCSF, a core facility that offers UCSF researchers access to modern small molecule discovery technologies including high-throughput screening, fragment-based drug discovery, and hit-to-lead medicinal chemistry. We have also built the Antibiome Center for generation of renewable recombinant antibodies to the proteome.